The chemistry of ion transport at the molecular level is understood only in quite general terms. The aim of this research is to enhance the understanding of rapid and selective ion transport through transmembrane channels at the molecular level. The gramicidin family of channels is a powerful system for investigating the interactions among ion, protein and lipid during the transport process. The gramicidin family represents a related series of peptides of known structure, in which specific changes in structure and the specific placement of polarizable substituents can be correlated with channel selectivity, stability, lipid dependence and transport properties. Advantages of the gramicidin family include: ideal selectivity for monovalent cations, partial intercationic specificity, single-file characteristics, its generally accepted structure, the availability of natural and synthetic analogues, and a sensitive assay for the equivalence of native and analogue conformations. This research will address the chemical control of the elementary steps of transport using both kinetic and equilibrium techniques. Site- specific modifications of the gramicidin channel will be used to (i) investigate channel properties and structure-function relationships, and (ii) design new molecular features that extend the function of the parent molecule. The results are expected to reveal general principles that govern ion transport through biological transmembrane channels, a process that is important for intercellular communication and for signal transmission in the nervous system.